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Biomedical subjects

Jonathan Benjamin

Publications and source records attributed to Jonathan Benjamin.

18 recordsLinked to original sources
PubMed2006

Power spectrum analysis and cardiovascular morbidity in anxiety disorders.

Spectral analysis of heart rate variability (HRV) and related measures has been shown to be a reliable noninvasive technique enabling quantitative assessment of cardiovascular autonomic regulatory responses to autonomic regulatory mechanisms; it provides a dynamic probe of sympathetic and parasympathetic tone, reflecting the interactions between the two. Over 20 studies reported abnormalities of HRV in anxiety, and patients with heart disease and anxiety are at increased risk for morbidity and mortality. Psychiatric drugs partly correct abnormalities of HRV and, recently, autonomic drugs (beta-blockers) have been studied in anxiety disorders. The authors call for further studies, especially in patients with co-existing anxiety disorders and heart disease, incorporating assessment of HRV.

Adrenergic beta-Antagonists↗
PubMed2006

Sensitivity to carbon dioxide in drug-naïve subjects with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is currently classified as an anxiety disorder in DSM-IV, and as a neurosis or stress-related disorder in ICD-10. It shares many features with depression. Sensitivity to carbon dioxide (CO2), a classic provocation agent in the proto-typical anxiety disorder, panic disorder, has not been tested in PTSD. Twenty rigorously ascertained drug-naïve subjects with PTSD inhaled a single vital capacity inhalation of 35% CO2; before and after the inhalation they completed measures of PTSD and panic anxiety, and were rated for the presence of a panic attack. These results were retrospectively compared with those of 39 healthy volunteers and 17 patients with panic disorder previously studied by the same research group. PTSD symptoms were not exacerbated by CO2. Two out of twenty PTSD subjects panicked. PTSD subjects' responses were indistinguishable from those of healthy volunteers, and differed from those of subjects with panic disorder. The lack of sensitivity to carbon dioxide in PTSD subjects in the present study adds to the literature on the differences between PTSD and other anxiety disorders, and to that on the specificity of the CO2 challenge in panic disorder.

Adult↗
PubMed2005

Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts.

Irradiation-resistant natural killer (NK) cells in an F(1) recipient can reject parental bone marrow, and host NK cells can also prevent engraftment of allogeneic bone marrow. We show here that repopulating bone marrow cells in certain mouse strains expressed retinoic acid early inducible 1 proteins, which are ligands for the activating NKG2D NK cell receptor. Treatment with a neutralizing antibody to NKG2D prevented rejection of parental BALB/c bone marrow in (C57BL/6 x BALB/c) F(1) recipients and allowed engraftment of allogeneic BALB.B bone marrow in C57BL/6 recipients. Additionally, bone marrow from C57BL/6 mice transgenic for retinoic acid early inducible 1epsilon was rejected by syngeneic mice but was accepted after treatment with antibody to NKG2D. If other stem cells or tissues upregulate expression of NKG2D ligands after transplantation, NKG2D may contribute to graft rejection in immunocompetent hosts.

Animals↗
PubMed2005

Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing to individual differences in an anxiety-related personality trait: TPQ harm avoidance.

The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety-related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region-wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 ( approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis.

Adult↗
PubMed2005

Effects of the cortisol synthesis inhibitor metyrapone on the response to carbon dioxide challenge in panic disorder.

Despite the well-known association between the hypothalamic-pituitary-adrenal (HPA) axis and normal fear, it is still unclear (a) to what extent corticotropin releasing hormone (CRH) or cortisol itself mediates fear responses, and (b) to what extent the HPA axis also affects panic disorder. The carbon-dioxide (CO2) challenge has been proposed as a model for panic. Participants received the cortisol synthesis inhibitor metyrapone 30 mg/kg of body weight once and placebo once, with 1 week between challenges, at 2300 h. The following morning, blood was taken for cortisol and ACTH levels, and then participants inhaled a single vital capacity inhalation of 35% CO2 and 65% oxygen. Before and after the inhalation, participants completed an inventory of the 13 DSM-IV symptoms of panic and the NIMH questionnaire of psychological and physical symptoms. Eight healthy controls and 14 patients with panic disorder completed the protocol. As expected, CO2 increased measures of anxiety, and metyrapone lowered cortisol and increased ACTH levels. Prechallenge anxiety was modestly lowered by metyrapone, but response to CO2 was not affected. Cortisol and ACTH levels before challenge partly predicted the response to CO2. The results support an anxiogenic role for cortisol in stress, and suggest that the pathophysiological mechanism that mediates CO2-induced panic differs from those underlying other kinds of anxiety.

Administration, Inhalation↗
PubMed2004

Sensitivity to carbon dioxide in subjects with a single lifetime panic attack: possible clinical "bedside" predictive test for panic disorder after a first attack.

There is currently no way of knowing whether a patient who has recently had a single panic attack has incipient panic disorder. Sensitivity to carbon dioxide (CO2) is lower in healthy volunteers than in panic disorder patients. If this is also true of people who experience a single lifetime panic attack, it could be used as a prognostic test. Subjects with a single lifetime panic attack and subjects with panic disorder received an inhalation of 35% CO2. Subjects completed the panic symptoms scale (PSS), and also stated whether they considered that they had experienced an attack. None of 14 subjects with a single lifetime panic attack, compared to 7 of 17 subjects with panic disorder (P=.009), had an attack. The PSS also distinguished between the groups. The 35% CO2 challenge warrants further investigation as a predictive test after a first panic attack.

Administration, Inhalation↗
PubMed2004

When patients run the show: the Sderot Psychiatric Center's Puppet Theater.

Psychiatric rehabilitation combats the damaging effects of mental illness on living, occupational and social skills, and strives to help patients lead creative and fulfilling lives. Medical and social changes, as well as financial pressure, have all increased the need for community rather than institutional rehabilitation. New philosophical emphases highlight patient self-actualization and empowerment. This paper describes the development of a puppet theater, whose members and artistic director are almost all chronic psychiatric patients; the project has achieved steady sheltered employment status and been awarded the first Zussman-JDC prize by the president of Israel. Interviews with patients elicited major differences between patient perceptions of traditional rehabilitation frameworks and the theater. Theater is more creative than typical sheltered employment opportunities for mental patients, and puppet theater has unique aspects that may be especially suited to their needs. Patients found participation an empowering experience.

Adult↗
PubMed2003

Tridimensional personality questionnaire trait of harm avoidance (anxiety proneness) is linked to a locus on chromosome 8p21.

Human personality traits are moderately heritable but only recently have specific polymorphisms been associated with particular personality dimensions especially anxiety-related and novelty-seeking traits. The first genome-wide scan for personality traits was recently carried out by Cloninger et al. [1998: Am J Med Genet 81:313-317] and his colleagues and they reported that a region on 8p21 showed linkage to TPQ Harm Avoidance, an anxiety-related personality trait. Towards replicating and extending these results, we examined both 8p21 and two additional chromosomal regions (1q21-24 and 22q12-13) for linkage to TPQ personality traits by genotyping at least three microsatellite markers in each region in a group of 384 sibling pairs. We found evidence for linkage to TPQ HA at 8p21-23 (Lod score = 2.907) confirming in an independent sample the initial findings by Cloninger and his colleagues.

Anxiety Disorders↗
PubMed2003

Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism.

OBJECTIVE: Studies have shown that genetic factors are significant in predisposing individuals to shyness and social phobia. Toward further elucidating the genetic structure of shyness, the authors examined four functional polymorphisms that make biological sense for contributing to the development of this phenotype: serotonin transporter promoter region 44 base pair insertion/deletion (5-HTTLPR), dopamine D(4) receptor exon III repeat (DRD4), catechol O-methyltransferase (COMT), and monoamine oxidase A promoter region repeat (MAO(A)). METHOD: The authors assessed shyness after recruitment of a nonclinical sample (N=118, unscreened second-grade children) using a composite scale derived from questionnaires administered to the children, parents, and teachers. DNA from buccal smears successfully obtained from 98 children was genotyped by polymerase chain reaction methods for the 5-HTTLPR, DRD4, COMT, and MAO(A) polymorphisms. RESULTS: Significant correlations were observed for parents', teachers', and children's ratings of shyness, and Cronbach's alpha reliability was high for all three scales. A significant association was observed between the long 5-HTTLPR polymorphism and shyness, both by the functional classification of Lesch as well as by consideration of all three genotypes. No significant association was observed for the DRD4, COMT, or MAO(A) polymorphisms. CONCLUSIONS: This study provisionally identifies a common genetic polymorphism, 5-HTTLPR, that modestly (effect size=7%) contributed to greater shyness scores in a nonclinical group of second-grade students. These first findings may be relevant to previous reports that have shown an association between the 5-HTTLPR long form and obsessive-compulsive disorder and autism.

Adult↗
PubMed2002

Personality genetics, 2002.

The study of the genetics of personality looks for effects of genetic differences on psychological differences between people. The most replicated associations have been between the dopamine D4 receptor gene and "novelty seeking" and between the serotonin reuptake transporter gene and anxiety. But even these reports are controversial, and their effects are too small to add to existing scientific theories or allow for clinical use in psychological counseling. Simultaneously studying three polymorphisms suggests that gene-gene interactions are partly responsible for these difficulties. Recently a linkage of anxiety-related traits to chromosome 8p21-23 has been replicated, and we may be close to isolating relevant genes in the region. But uncertainty about psychological phenotypes remains, and it is not clear whether future breakthroughs will require studies of thousands of genes in very large samples, or revolutions in the current assumptions and methods of personality genetics.

Genetic Linkage↗
PubMed2002

An update on molecular genetic studies of human personality traits.

Personality is a complex phenotype and people differ considerably when they are evaluated by self-report questionnaires. There is convincing evidence from twin studies that basic personality dimensions in men and women have a considerable genetic component. However, only recently have common genetic polymorphisms been associated with particular personality traits, especially the dopamine D4 receptor with novelty seeking and the serotonin transporter with anxiety-related traits or neuroticism. The current review examines progress in the past few years in molecular personality genetics and focuses on the reasons for difficulties in replicating first findings as well as the prospects for future studies in this area. The molecular genetic structure of human personality is worth studying both for its intrinsic interest in helping us to understand individual differences in human behaviour and the light it will shed on more complex behavioural disorders that are likely to partially share some common genetic variants.

Animals↗
PubMed2001

Lack of association between joint hyperlaxity and, I: panic disorder, and II: reactivity to carbon dioxide in healthy volunteers.

This study attempted to replicate previous reports of associations between panic disorder and joint hyperlaxity. The authors also examined possible associations between reacitivity to carbon dioxide (CO(2)), a model for panic vulnerability, and hyperlaxity in healthy volunteers. One hundred and one patients with DSM-IV panic disorder and 39 healthy volunteers were assessed for hyperlaxity by Beighton's criteria. Healthy volunteers also received two vital capacity inhalations of CO(2). Thirteen (13%) patients had five or more hyperlax joints. This rate did not differ from that in the healthy volunteers. Anxiety in healthy volunteers, as measured by the NIMH self-rating scale, DSM-IV panic symptom scores, and 100 mm visual analog scales of anxiety, increased after CO(2) from a mean of 1.8 to 2.8 (not significant); from 0.5 to 4 ( p < 0.001) and from 8.7 to 11.6 mm ( p < 0.1), respectively. There were no associations between responses to CO(2) and hyperlaxity. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2001

Influence of the serotonin antagonist, metergoline, on the anxiogenic effects of carbon dioxide, and on heart rate and neuroendocrine measures, in healthy volunteers.

The mechanism of action of carbon dioxide (CO(2)) angiogenesis is unknown; only recently have possible serotonergic (5-HT) influences begun to be studied. In separate double-blind challenges 1 week apart, 14 healthy volunteers received two vital capacity inhalations each of 35% CO(2) and of air, once after a single capsule of placebo and once after a single capsule containing 4 mg of the 5-HT antagonist metergoline in a randomized crossover design. The inhalations were repeated 1 and 2 days after the ingestion of capsules, to investigate possible delayed effects of metergoline, and possible tolerance to repeated CO(2) after placebo. We observed increased anxiety, and a trend for increased plasma noradrenaline (NA), after CO(2). CO(2) anxiogenesis was significantly enhanced by metergoline. Heart rate increased after both gas mixtures following metergoline administration. Plasma prolactin levels were lower after metergoline. Responses to CO(2) did not differ between the day of placebo administration and the two subsequent days; on the days following metergoline administration there were almost no delayed effects. We hypothesize that 5-HT may function as an inhibitor of CO(2) anxiogenesis, and that this is opposed by the 5-HT antagonist, metergoline. Absence of tolerance after repeated CO(2) argues against psychological explanations of tolerance after other panicogens. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder: a double-blind cross-over study.

Current serotonin reuptake inhibitor (SRI) treatments for obsessive-compulsive disorder (OCD) provide only partial benefit. A previous study suggested that inositol alone is efficacious in OCD. Ten DSM-IV OCD patients completed a study of 18 g inositol or placebo for 6 wk each in addition to ongoing SRI treatment in a double-blind randomized cross-over design. Weekly assessments included the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety scales. No significant difference was found between the two treatment phases.

Journal Article↗
PubMed1998

Genes for personality traits: implications for psychopathology.

Although 30-60% of the variance in many personality traits is inherited, until recently, little was known about the genes responsible. Preliminary studies of family history in bipolar disorder and of X-linkage of personality traits in colour-blindness suggested a 'quantitative trait locus' (QTL) approach to the genetics of normal personality. In methodically similar but independent studies of 124 Israeli and 315 American normal volunteers, an association was found between the dopamine D4 receptor gene (D4DR) and the personality trait of novelty-seeking. In the Israeli sample there was preliminary evidence for an interaction between the D4DR gene and the serotonin 2C receptor gene (5-HT-2C), with a marked effect on the trait of reward dependence. In addition to receptors, monoamine uptake mechanisms, such as the serotonin transporter (5-HTT), are candidate genes for personality traits. 5-HTT gene transcription is modulated by a frequent polymorphism in its promoter region, with resulting effects on 5-HTT expression and 5-HT uptake. In an extended American sample totalling 505 subjects, the 5-HTT polymorphism was associated with anxiety- and depression-related personality traits. The allelic variation in functional expression of the 5-HTT may also be a susceptibility factor for disorders of the affective spectrum. Further investigation of genes for personality traits may provide additional links between normal personality and psychiatric illness.

Journal Article↗
PubMed1991

Remission of Tardive Dystonia with ECT.

A 30-year-old patient with tardive dystonia, who had failed to respond to cessation of neuroleptics, placebo, diazepam, biperiden, propranolol, and clonidine, had an impressive response to courses of electroconvulsive therapy (ECT) on three successive trials.

Journal Article↗